CTC and ctDNA

MyGenome

2.1 CTC and ctDNA

  • In the last several years, both academic and commercial researchers published reports about finding circulating DNA in earlier stage cancers.
  • Many of the studies are trying to solve the same problems, with researchers using different technologies and approaches.
  • Researchers discovered how to find and study circulating tumour DNA (ctDNA).
  • Before using tumour DNA to find and evaluate earlier stages of cancer, this technology was used to monitor patients after they received treatment for an advanced cancer.
  • ctDNAs are tiny fragments of DNA in the blood that break away from tumours. After treatment, the ctDNA levels decrease because the tumour is either smaller or has been removed.
  • Researchers monitored ctDNA levels in blood to watch for increases over time and realised they could see an increase in the ctDNA several months before they could visibly see a recurrence of cancer.
  • The ctDNA sort of acts like a vacuum cleaner, bringing together all the DNA fragments and finding other mutations that may be elsewhere.
  • Researchers are also exploring ways to identify where the cancer may be. The goal is to use the cell-free DNA in the blood to learn that a person may have cancer somewhere in the body before it’s easily visible by current techniques, such as colonoscopy, mammography, x-rays, or CT-scans.
  • With that combination, the cell-free DNA allowed researchers to sort for circulating tumour DNA and detect mutation that suggests cancer.
  • The first description of circulating DNA free from cells in human blood was in 1948, but this garnered little attention in the broader scientific community.
  • In 1977, scientists identified the presence of abnormally high levels of cell-free DNA (cfDNA) in the plasma and serum of cancer patients relative to health control patients and this cfDNA was presumed to represent mainly circulating tumour DNA (ctDNA).
  • Since this original description, other research has found that increased cfDNA generally reflects a multitude of pathologic processes, including malignant and benign neoplastic conditions, inflammatory diseases, stroke, trauma, and sepsis.
  • During these processes, nucleic acids may be shed into the blood by apoptotic and necrotic cells or by controlled secretion by living cells.

The molecular analyses enabled by isolation of CTCs and cfDNA in liquid biopsies may be applied to guide different treatment strategies at different events in the initial diagnosis and treatment of patients with cancer (Figure).

SCREENING FOR PRESENCE OF DISEASE;

PATIENT STRATIFICATION AND THERAPY SELECTION (COMPANION DIAGNOSTICS);

MONITORING TREATMENT RESPONSE AND DRUG RESISTANCE; AND

DETECTION OF MINIMAL RESIDUAL DISEASE AFTER SURGERY/RECURRENCE.